Abstract TAC220: Effect of Hesperidin Intake on Blood Pressure and Gut Microbiota Composition in 2-Kidney, 1-Clip Renovascular Hypertensive Rats

Introduction: We previously reported that hesperidin intake reduces blood pressure (BP) in 2-kidney, 1-clip renovascular hypertensive model (2K1C) rats. Hesperidin is a kind of polyphenol found in citrus peels, and was reported to contribute to the proliferation of bacteria such as Bifidobacterium spp ., Lactobacillus spp ., and Akkermansia muciniphila , which produce short-chain fatty acids (SCFAs). SCFAs such as acetic acid, butyric acid and propionic acid, have been reported to lower BP in hypertensive model animals. However, to our knowledge, there have been no studies that observed changes in their gut microbiota in hypertensive model animals when administered hesperidin. Hypothesis: Hesperidin partially alters gut microbiota, especially with an increase in SCFA-producing bacteria in 2K1C rats. Methods: Sham-operated control model (SHAM) or 2K1C were induced in six-week-old Sprague Dawley rats under anesthesia. Both rat models were made to ingest a control diet (CTL) or a 0.1% (0.1 of 100, w/w) hesperidin including diet (Hes), and to access a drinking water freely for 6 weeks. During the feeding, rats were observed systolic BP (SBP) by tail-cuff method weekly. After euthanasia, the cecal contents were collected and analyzed for microbiota by 16S rRNA amplicon sequencing V3-V4 hypervariable regions. P < 0.05 was considered statistically significant. Results: Six weeks after surgery, the SBP was significantly higher in 2K1C-CTL than that of SHAM-CTL (178 ± 5 vs 133 ± 3 mmHg, P < 0.001) and was significantly lower in 2K1C-Hes (158 ± 2 mmHg, P < 0.01) than that of 2K1C-CTL. In SHAM, there was no significant difference in SBP between CTL and Hes groups (133 ± 3 and 132 ± 3 mmHg). The Kruskal-Wallis test revealed significant differences in the relative abundance of Eubacterium , Acetitomaculum and Blautia among 4 groups: SHAM or 2K1C rats fed CTL or Hes . Subsequently, post-hoc tests showed that the relative abundance of Acetitomaculum and Blautia were significantly increased in 2K1C-Hes compared with 2K1C-CTL. Because Acetitomaculum and Blautia are SCFA-producing bacteria, their increases may contribute to the suppression of BP elevation in 2K1C rats. Conclusions: Hesperidin intake partially altered the gut microbiota in 2K1C rats, with a significant increase in SCFA-producing bacteria including Acetitomaculum and Blautia .